Food Chemicals Codex 5th Edition

FIFTH EDITION

FOOD

CHEMICALS

CODEX

Effective January 1, 2004

C

OMMITTEE ON

F

OOD

C

HEMICALS

C

ODEX

Food and Nutrition Board

THE NATIONAL ACADEMIES PRESS

•

500 Fifth Street, N.W.

•

Washington, DC 20001

NOTICE:The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose

members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

Support for this project was provided by U.S. Food and Drug Administration Contract No. 223-99-2321. The views presented in this report are those of the Institute of Medicine Committee on Food Chemicals Codex and are not necessarily those of the funding agency.

COMPLIANCE WITHFEDERALSTATUTES The fact that an article appears in the Food Chemicals Codexor its supplements does not

exempt it from compliance with requirements of acts of Congress, with regulations and rulings issued by agencies of the United States Government under authority of these acts, or with requirements and regulations of governments in other countries that have adopted theFood Chemicals Codex. Revisions of the federal requirements that affect theCodexspecifications will be included in Codexsupplements as promptly as practicable.

Library of Congress Cataloging-in-Publication Data

Food chemicals codex / Committee on Food Chemicals Codex, Food and Nutrition Board, Institute of Medicine.-- 5th ed.

p. cm.

‘‘Effective January 1, 2004.’’ Includes index.

ISBN 0-309-08866-6 (hardback)

1. Food additives--Standards--United States. 2. Food additives--Analysis. I. Institute of Medicine (U.S.). Committee on Food Chemicals Codex.

TP455.F66 2003

664′.06′021873--dc21 2003010423

Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.

For more information about the Institute of Medicine, visit the IOM home page at:www.iom.edu. Copyright 2003 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America.

No part of this publication may be reproduced by any mechanical, photographic, or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use, without written permission from the publisher, except for official use by the United States Government or by governments in other countries that have adopted theFood Chemicals Codex.

THE NATIONAL ACADEMIES

Advisers to the Nation on Science, Engineering, and Medicine

The National Academy of Sciencesis a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences.

The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering.

TheInstitute of Medicinewas established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.

TheNational Research Councilwas organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org.

COMMITTEE ON FOOD CHEMICALS CODEX

S. Suzanne Nielsen(Chair2001− );Vice-Chair (1998−2000), Department of Food Sci-ence, Purdue University, West Lafayette, IN

Grady W. Chism III(Vice-Chair2001− ) Department of Food Science and Technology, Ohio State University, Columbus

Michael H. Auerbach, Danisco USA, Inc., Ardsley, NY Jonathan DeVries, General Mills, Inc., Minneapolis, MN Mark Dreher, McNeil Nutritionals, New Brunswick, NJ Carl Frey, Pepsi Cola North America, Valhalla, NY David S. Frick, Sensient Colors, Inc., St. Louis, MO Glen Ishikawa, NutraSweet Company, Evanston, IL

Richard W. Lane, Unilever Bestfoods NA, Englewood Cliffs, NJ John W. Salminen, Health Canada, Ottawa, Ontario, Canada

Shelly J. Schmidt, Department of Food Science and Human Nutrition, University of Illinois at Champaign-Urbana

Pamela J. White, Food Science and Human Nutrition Department, Iowa State Univer-sity, Ames

Consultant

Andrew G. Ebert, The Kellen Company, Atlanta, GA

Staff

Ricardo A. Molins, Study Director (1999− ) Marcia S. Lewis, Research Assistant

FORMER MEMBERS AND STAFF OF THE COMMITTEE ON FOOD CHEMICALS CODEX, 1998–2003

Andrew Ebert, 1988−1999 E. Allen Foegeding, 2000−2001 Merle Pierson, 1998−2001 Steve Taylor, 1989−2000 George Zografi, 1995−1999

Fatima N. Johnson, Study Director (1992−1999) Maria Oria, Program Officer (2002−2003)

FOOD AND NUTRITION BOARD MEMBERS

Robert M. Russell(Vice-Chair), Jean Mayer USDA Human Nutrition, Research Center on Aging, Tufts University, Boston, MA

Larry R. Beuchat,Center for Food Safety, University of Georgia, Griffin

Benjamin Caballero,Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

Shiriki Kumanyika, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia

Lynn Parker,Food Research and Action Center, Washington, DC

A. Catharine Ross,Nutrition Department, Pennsylvania State University, University Park Barbara O. Schneeman,Department of Nutrition, University of California, Davis Steve L. Taylor,Department of Food Science and Technology, University of

Nebraska-Lincoln

Catherine E. Woteki,Iowa State University, Ames

Barry L. Zoumas, Alan R. Warehime Professor of Agribusiness, Department of Agricultural Economics and Rural Sociology, Pennsylvania State University, University Park

Staff

Allison A. Yates,Director Linda Meyers,Deputy Director Gail Spears,Administrative Assistant

Geraldine Kennedo,Administrative Assistant Gary Walker,Financial Associate

Participants in Committee Activities and Other Programs

Workshop on Criteria for Establishing Microbiological Specifications for Food Additives

(April 25, 2000)

Gary Acuff Rodney Gray

Dane Bernard Ricardo Molins Robert Buchanan Merle Pierson Richard Ellis Steve Taylor Russell Flowers Bruce Tompkin

Others Who Provided Assistance, 1998–2003

Nancy Alexander Robert G. Bursey

Gideon Andemicael Stephen J. Byrd Roger Dabbah

Ben Andreson Christine Daley

Jit F. Ang Edward Campbell Alberto Davidovich Stephen Ashmead Michael F. Campbell A. de Groot Mohamed Bakri Assoumani Richard Cantrill John Dean Michael H. Auerbach Janet Catanach Michael E. Deiker J. Ayala Claudia Ceniceros G. Christopher C. DeMerlis

Marilyn R. Chambers Laura Depinto K. V. Balakrishnan Noeline Champion Mario Diaz-Cruz, III Richard L. Barndt Sharon Chang Sidney A. Doode Charles H. Barnstein Minn-Chang Cheng Jim Doucet Julie N. Barrows Zak Chowhan James E. Downes Klaus Bauer Eunice Ciurlie Paul Dribnenki A. Allen Bednarczyk James P. Clark Douglas A. Drogosh Alison R. Behling Ross Clark G. Duchateau Gint Behreus Ryan M. Clark John Dutton Raffaele Bernetti Warren S. Clark, Jr.

Bruce M. Bertram Margaret Clarke Andrew Ebert J. Bertram David B. Clissold Denise L. Edgren Sanford W. Bigelow Melissa Cockayne Karen Elam Robert Biles Kipp A. Coddington James T. Elfstrum Anthony T. Bimbo David Cook Richard Ellis Don Blaine Jerry Cook Sheryl E. Ellis Mel Blum Steven J. Cooke Mark Empy Cheryl Borders C. Arleen Courtney Roy Engels Don P. Boudreaux Stuart Craig Elizabeth Erman Marion M. Bradford Richard E. Cristol

Kyd Brenner Raymond V. Croes H. Fallahi Phillip R. Bross Eunice Cuirle John Fernstrom Paul Browning Lance Culbert Peg Fitzkee

viii / Participants in Committee Activities FCC V

Thomas Fletcher Steven E. Hill Laurent Leduc Patrick T. Flynn, Jr. Annet Hoek Ingrid Leutritz Barbara Ford Pat Hoffman Greg Lima

George T. Ford, Jr. Ronald D. Hogue Gerard E. Linkowski John V. Fratus Thomas Holland Clara Lubarsky

John Fry James How Po Yam Lui

James Hyde

Raymond J. Maggio James A. Gall

Vicente Iban˜ez Robert Maloney Debbie Garczynski

Kenji Ishii Steven Manheimer Jerry D. Gargulak

Mark L. Itzkoff Clodualdo Maningat Paula Gaynor

Ody Maningat Joe Gensic

K. James _{Colin D. May} Gerstner Gerhard

Jay-lin Jane _{James P. McCarthy} Tammy Gierke

Allen J. Johnson _{Diane B. McColl} Kevin Gillies

Jerry Jost _{Gary McDermott} John P. Gleason

David R. Joy _{Larry McGirr} Victor C. Go

Hamish Joyce _{Bill McKeown} Mary A. Godshall

Mike McLean Amy R. Goodfellow _{Isabelle Kamishlian}

Irving Melcer Scott J. Grare _{Ken Kasengrande}

Doug J. Melton Rodney J. H. Gray _{Robert Kasik}

Philip H. Merrell Richard Green _{G. Kere Kemp}

Rich Milito James Griffiths _{Gregory Kesel}

Philip Mingle Lisa Gruener _{Ken Keyte}

Mel Mirliss Janeen Kincaid

Dewey Mitchum Martin Hahn _{Charles L. King}

M. Miyasaka Mikyoung Hahn _{P. P. Kirsch}

John Modderman Ferid Haji _{Lori L. Klopf}

Bill Monagle John Hallagan _{Christian Klug}

Thomas J. Muldoon Earl G. Hammond _{W. F. Kohl}

G. Mu¨ller Sue Harris _{Monique Kosse}

Raja K. Murti M. Hashimoto _{Karen Kowalewski}

Amy Mutre Christopher D. Hassall _{Paul Kuznesof}

Ken Hassan _{Carol Kyck}

Lyn Nabors Theodore D. Head

Denise Nahon Jerome H. Heckman Ron Lacock

Donald D. Naragon Allan R. Hedges Frank Lambert

June M. Neades Barbara B. Heidolph William Lambert

Lisa Nevarro Richard Hendricks Lucina Lampila

Michael Henkel Kathleen E. Lanshe

Melanie O’Donnell Bruce Henkin Richard Larock

Atsuhi Okiyama John L. Herrman Susan Lawlor

Owen J. Olesen Joseph Hickenbottom Brian Lawrence

Stanley T. Omaye David H. Hickman Neil Lawson

Aydin O¨ rstan J. J. Higgins Patricia L. Lawson

FCC V Participants in Committee Activities / ix

Juhani Paakkanen Sheldon Silbiger Lorraine Twerdok Andy Paterson John M. Simmons R. T. Tyler Ken Paydon Patrick Smith Tom Tyner John Pearce Timothy R. Smith

Bruce Peterson Elisabeth A. Snipes Youichiro Umeki Bruce E. Phillips Jennifer Snyder

Glyn O. Phillips Charles Sokol Q. Edith Valle C. Jay Piester Kyle A. Spencer Mel Vandenberg

Laura M. Spiegelhoff Cheryl Van Dyne Glenn A. Rasmussen Jennifer Spokes Julio C. Vega Gregory Redko Erik Sprenne James Verghese Dorothee Reuscher Edward A. Steele Marc Vermaeulen Greg Reynhout Daniel G. Steffen Uwe Voekler Alan B. Richards Lewis Stegink Wolfgang A. Vogl Michelle Rieckhoff Fred Stone Frank Vollaro William Riha David Straus

Chet A. Roberts Eric Strauss Robert Waller, Jr. Mark Robertson Hiroshi Sugano Glenn Ward Susan Rodgers Yoshi-hisa Sugita Cayce Warf Bryan Rodriguez Rusell Sydes Jerry Weigel Quinton Rogers Bernard F. Szuhaj Cathy Wendler

Glenn Ruskin Richard H. Wendt

Robin A. Russell Tetsua Taguchi Thomas P. West, Jr. Todd Talashek Jennifer White George Sanderson David A. Tarizzo Stephanie Winder Antonio Sardella Sarah Taylor Karen Wingartz Eiji Sato Steve Taylor John T. Woodard David A. Saunders Taguchi Tetsuya Hennie A. Workel Rudolph F. Scarpelli Jette Thestrup Karel Wright Kevin Schaffler Rani M. Thomas William W. Wright Rainer Schnee William R. Thornton

Ed Schoenberg Geoff Tomlinson Kohei Yamamoto Michael Schrage Josephine M. Torrente Gary L. Yingling Gloria T. Seaborn Kathleen Trahanovsky Matt Yokota Catherine Sheehan Keith Triebwasser

Paul E. Shelton Bryan Tungland Priscilla S. Zawislak Tadahisa Shimoda Samuel Tuthill Randall E. Zigmont

Preface

The Fifth Edition of theFood Chemicals Codex (FCC) is a result of the collective efforts of the many members, past and present, of the Committee on Food Chemicals Codex over the past 42 years. The current committee, whose members have brought all these efforts to fruition with this edition, was appointed following a request from the U.S. Food and Drug Administration (FDA) to continue this activity. The charge to the committee states that ‘‘the committee shall (1) provide information on matters related to the purity of food ingredients used in the United States and shall be knowledgeable of the purity of food ingredients used in other countries; (2) provide information on food-grade specifications for food additives, GRAS [generally recog-nized as safe] substances, and any other food substances used as ingredients; and (3) publish specification monographs in a Fifth Edition of the Food Chemicals Codex. To provide such information, the committee shall review proposals from industry, government, and any other source.’’

The FCC project, currently under the Food and Nutrition Board of the Institute of Medicine of the National Academies, began in 1961, soon after the passage of the 1958 Food Additives Amendment to the federal Food, Drug, and Cosmetic Act. Although the FDA had, by regulations and informal statements, defined in general terms the quality requirements for GRAS and other food chemicals, these requirements were not sufficiently specific to serve as release, procurement, and acceptance specifi-cations for manufacturers and users of food chemicals. Therefore, regulators and other interested parties believed that the publication of a book of standards designed especially for food chemicals would promote uniformity of quality and added assur-ance of safety for such chemicals. For these reasons, the Food Protection Committee of the National Academy of Sciences/National Research Council received requests in 1958 from its Industry Liaison Panel and other sources to undertake a project to produce aFood Chemicals Codexcomparable in many respects to theUnited States Pharmacopeia and theNational Formularyfor drugs. As a result of these requests, representatives of industry and government agencies agreed that there was a definite need for such aCodexand that the Food Protection Committee was a suitable body to undertake the project.

xiv / Preface FCC V

The first edition, published in 1966, was supported by a Public Health Service grant and more than 100 supplementary grants from industry, associations, and founda-tions. Its role, which is still that of the Food Chemicals Codex, was to define the quality of food-grade chemicals in terms of identity, strength, and purity based on the elements of safety and good manufacturing practice. Later editions were supported by direct contracts with the FDA. Such sponsorship has been sufficient to support the publication of 4 earlier editions and 14 supplements in a 42-year span.

SCOPE

The scope of the Food Chemicals Codex has expanded with each new edition. Substances included in the first edition were limited to chemicals added directly to foods to achieve a desired function. Succeeding editions included these substances as well as such processing aids as enzymes, extraction solvents, filter media, and boiler water additives; those that are regarded as foods, such as fructose and dextrose, rather than as additives; and those that exhibit a functional effect, not on the foods to which they are added, but to the human body when the food is consumed. This Fifth Edition includes 961 monographs from the Fourth Edition; 49 monographs, along with those for 15 flavor chemicals, added in the three supplements to the Fourth Edition; and 19 new monographs, along with 33 for flavor chemicals, new to this Fifth Edition, bringing the total to 1077. Because of its regulatory status in countries other than the United States, and its worldwide use, the Food Chemicals Codex contains some monographs for chemicals not currently allowed in foods in the United States. This circumstance is clearly indicated in such monographs.

UPDATING AND DEVELOPING SPECIFICATIONS

FCC V Preface / xv

Limits on contaminants, specifically lead and other heavy metals, have been reduced in most monographs in this edition. This trend is expected to continue. Manufacturers and suppliers of food ingredients are encouraged to inform the committee of their ability to supply food ingredients with lead and other heavy metals limits lower than those specified in this edition. The arsenic specification remains in relatively few monographs in this edition where (1) the ingredient or additive is a high-volume consumption item (greater than 25 million pounds a year), (2) the ingredient or additive is derived from a natural (mineral) source where arsenic may be an intrinsic contaminant, or (3) there is reason to believe that arsenic constitutes a significant part of the total heavy metals content.

The committee is cognizant of the need for international harmonization of tions in today’s world. Efforts were made, where feasible, to harmonize the specifica-tions in this edition with those of other standards-setting organizaspecifica-tions, in particular with those in theCompendium of Food Additive Specifications, prepared by the Food and Agricultural Organization of the United Nations (FAO)/World Health Organiza-tion (WHO) Joint Expert Committee on Food Additives (JECFA) and published by the FAO.

FORMAT

Generally the presentation follows that of the Fourth Edition, but a number of signifi-cant changes and additions have been made. As expected, the passage of 7 years since the appearance of the Fourth Edition has been accompanied by changes:

T Additional information in terms of FEMA (Flavor and Extract Manufacturers Asso-ciation) numbers has been added to essential oil and other flavor monographs not in the Flavors Table, Chapter 3.

T Infrared Spectra for most substances requiring them for identification purposes have been rerun and thus are more accurate.

T New headers on each page of this book tell readers where they are by chapter, monograph, appendix, or test.

T The language in the monograph section has been revised to be more clear, consistent, and concise.

T All tests that occurred identically in three or more monographs were moved to the appendices.

FUTURE REVISIONS

The introduction of new food additives as well as constant changes and advances in manufacturing processes and analytical sciences lead to a need for continued revision of this compendium.

xvi / Preface FCC V

access to such advanced technology. The committee specially recognizes the urgency of updating current chromatographic methods throughout the present edition and intends to complete this goal during the next 5 years. Users of this edition are requested and encouraged to submit suggestions for updating the specifications as well as the general analytical methods. Constructive criticism and notification of errors should also be brought to the attention of the Food Chemicals Codex, Institute of Medicine, 500 Fifth Street, N.W., Washington, D.C. 20001 or <fcc@nas.edu>.

LEGAL STATUS

The Food Chemicals Codexhas earned international recognition by manufacturers, vendors, and users of food chemicals. The specifications herein serve as the basis for many buyer and seller contractual agreements.

In the United States, the first edition was given quasi-legal recognition in July 1966 by means of a letter of endorsement from FDA Commissioner James L. Goddard, which was reprinted in the book. The letter stated that ‘‘the FDA will regard the specifications in the Food Chemicals Codexas defining an ‘appropriate food grade’ within the meaning of Sec. 121.101(b)(3) and Sec. 121.1000(a)(2) of the food additive regulations, subject to the following qualification: this endorsement is not construed to exempt any food chemical appearing in theFood Chemicals Codexfrom compliance with requirements of Acts of Congress or with regulations and rulings issued by the Food and Drug Administration under authority of such Acts.’’

Subsequently, the specifications in the Second Edition, followed by those in the Third Edition, were cited, by reference, in the U.S.Code of Federal Regulationsto define specific safe ingredients under title 21, in various parts of sections 172, 173, and 184.

In Canada, the current edition of theFood Chemicals Codex, including its supple-ments, is officially recognized in the Canadian Food and Drug Regulations under Section B.01.045(b) as the reference for specifications for food additives. The new Australia New Zealand Food Authority recognizes the Food Chemicals Codex as a primary source of identity and purity specifications in its Food Standards Code, Chapter 1 General Food Standards, Part 1.3 Substances Added to Food, Standard 1.3.4 Identity and Purity.

REVIEWERS

FCC V Preface / xvii

William E. Artz, University of Illinois James N. Bemiller, Purdue University

Rengaswami Chandrasekaran, Purdue University Sam Chang, North Dakota State University Susan L. Cuppett, University of Nebraska Stephanie Doores, University of Pennsylvania

William Eigel, Virginia Polytechnic and State University Ronald Eitenmiller, University of Georgia

Jeffrey M. Farber, Health Canada Harold R. Faust, Penreco

Kenneth Fowkes, Praxair Distribution Inc. Earl Hammond, Iowa State University Donald L. Johnson, Consultant Paul Lachance, Rutgers University

John Lichtfield, The Ohio State University

Harold M. McNair, Virginia Polytechnic and State University Dennis D. Miller, Cornell University

David B. Min, The Ohio State University

Sean O’Keefe, Virginia Polytechnic and State University Andrew Proctor, University of Arkansas

Jenny Scott, National Food Processors Association Randy Wehling, University of Nebraska

Ronald Wrolstad, Oregon State University

Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Barbara P. Klein, University of Illinois. Appointed by the National Research Council and Institute of Medicine, she was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

ACKNOWLEDGMENTS

A compendium of this breadth can only result from the cooperation of many individuals and organizations. Underlying this, the support provided by FDA contract number 223-99-2321, monitored by project officers Paul M. Kuznesof and Daniel Folmer, is gratefully acknowledged.

xviii / Preface FCC V

(BAM) for its microbial limit tests. Where the sample size is not defined in the limit, the results are based on the sampling procedures described in BAM.

While participating individuals have been listed on pages vii–ix, the following organizations have also been active participants:

American Dairy Products Institute Corn Refiners Association Enzyme Technical Association

Flavor and Extract Manufacturers Association Gelatin Manufacturers of Europe

Gelatin Manufacturers Institute of America International Association of Color Manufacturers International Dairy Federation

International Food Additives Council International Pectin Producers Association International Pharmaceutical Excipients Council International Technical Caramel Association

National Association of Chewing Gum Manufacturers Salt Institute

Soy Protein Council

Members of the National Academies Press—Sally S. Stanfield, James M. Gormley, Estelle H. Miller, Dan Parham, and William B. Mason—and staff of the Institute of Medicine Office of Reports and Communication—Jennifer Bitticks, Jennifer Otten, Bronwyn Schrecker, and Leah Covington—provided valuable support to the FCC staff toward the publication of this edition.

Success in the complex task of completing the Fifth Edition is due to the dedication and determination of the members of the Committee on Food Chemicals Codex under the focused leadership of its successive chairs, Steve L. Taylor and S. Suzanne Nielsen, during the past 58 months, and to those of the Food Chemicals Codex staff, Maria Oria and Marcia Lewis.

Washington, D.C. Ricardo A. Molins

General Information

OPERATING PROCEDURES OF THE FOOD CHEMICALS CODEX

Organization

The Food Chemicals Codex (FCC) project is an activity of the Food and Nutrition Board, a unit of the Institute of Medicine of the National Academies. The immediate responsibility for developing theFood Chemicals Codexlies with the Board’s Commit-tee on Food Chemicals Codex. The commitCommit-tee consists of 12 to 15 members, chosen for their expertise in the various aspects of the committee’s work, who are appointed, upon recommendation of the Food and Nutrition Board and the President of the Institute of Medicine, by the Chairman of the National Research Council. Committee members are paid no consulting fees or honoraria and are reimbursed only for expenses incurred while attending meetings and other activities of the committee.1

Functions of the Committee on Food Chemicals Codex

The committee’s principal functions are as follows:

T To establish the general policies and guidelines by which FCC specifications are prepared.

T To evaluate comments submitted by interested parties on any aspect of the specifica-tions and test procedures.

T To propose means by which the specifications may be kept current in reflecting food-grade quality on the basis of product safety and good manufacturing practices. T To provide information on issues dealing with specifications for particular sub-stances and analytical test procedures.

1_{The project scope, a committee roster, and meeting information are accessible on the National Academies’}

web site. Access <www.nationalacademies.org/cp.nsf> and search by name for ‘‘Food Chemicals Codex.’’

xx / General Information FCC V

T To seek the advice of specialists when additional expert opinion is needed in making decisions regarding the appropriateness of specifications.

T To establish working groups consisting of committee members and other experts to address specific issues relevant to monograph development and to report their findings and recommendations to the full committee.

T To consider and act on any other issues concerning the development and publication of specifications and test procedures for food-grade ingredients.

T To approve the final manuscript for review before the publication of any edition of the FCC or its supplements.

Committee business is conducted through a central office at the National Academies in Washington, D.C. The appointed responsible study director at the Food and Nutrition Board, Institute of Medicine, coordinates all committee activities. The committee meets in regular session, usually once a year, to discuss the project’s progress, including technical and policy issues relevant to the FCC. One or more members of the committee as well as the study director conduct ad hoc meetings on short-term projects as needed. The committee and study director also organize workshops and symposia as appropriate to exchange information with interested parties on key issues, whether of broad or limited scope.

Requirements for Listing Substances in theFood Chemicals Codex

The requirements are as follows: (1) the substance is permitted for use in food or in food processing in the United States (or, in certain cases, in other countries in which FCC specifications are recognized), (2) it is commercially available, and (3) suitable specifications and analytical test procedures are available to determine its identity and purity.

Criteria for Food Chemicals CodexGrade

FCC V General Information / xxi

presence of which would be inconsistent with GMP. This matter is discussed further underTrace Impurities, in theGeneral Provisions, and underGeneral Good Manufac-turing Practices Guidelines for Food Chemicals.

In addition to impurity limits, specifications, where applicable, must include the following: empirical formula, structural formula, and formula weight; description of the substance, including physical form, odor (flavoring agents only), and solubility (see the descriptive terms for solubility in the General Provisions); identification; assay (or a quantitative test to serve as an assay); physicochemical characteristics such as specific rotation, melting range or solidification point, viscosity, specific gravity, refractive index, and pH; loss on drying or water content; residual solvents; limits for mycotoxins and microbiological contaminants; and limits for byproducts and other adventitious constituents usually occurring in, or arising from the manufacture of, the substance. For safety, the committee deleted taste, as a characteristic of any substance, from all monographs, and odor from all but flavor monographs. The data provided, taken together, represent a complete compositional understanding of the substance. Additional information items include how the substance is to be packaged and stored to maintain its integrity and its functional use(s) in foods. If the substance contains an ‘‘added substance,’’ mentioning this fact enables the committee to judge whether the specifications should include it (see Added Substances under General Provisions).

Important Changes That May Affect How Information Is Submitted

Before submitting information to the Committee on Food Chemicals Codex, please read carefully the following paragraphs about the Federal Advisory Committee Act (FACA) Amendments of 1997, section 15, public law number 105-153. This act creates certain new requirements regarding studies performed for federal government agencies by the National Academies: the National Academy of Sciences (NAS), the National Academy of Engineering (NAE), the Institute of Medicine (IOM), and the National Research Council (NRC) (collectively referred to as ‘‘the National Academies’’).

The National Academies’ policy applies to any committee (board, panel, etc.) appointed by the National Academies to develop a report (study reports, letter reports, workshop proceedings, summaries of symposia, and other manuscripts derived from institutional activities) that is intended for distribution outside the National Academies.

xxii / General Information FCC V

Documents Unavailable to the Public at Committee Meetings Any committee meeting at which only committee members and officials, agents, and employees of the National Academies are present is a ‘‘closed committee meeting.’’ Closed committee meetings are not open to the public or to any person who is not a committee member or an official, agent, or employee of the National Academies. Deliberations by a committee in discussing, preparing, and finalizing a draft written report, including deliberations relating to review comments received in connection with review of the draft report under the National Academies’ report review process, must be conducted in closed meetings.

After each closed committee meeting, the study director for the committee shall prepare a brief summary of the closed committee meeting and post the summary immediately on the National Academies’ web site <www.nas.edu>. Except as provided by the exemptions, the brief summary of a closed committee meeting will identify the committee members present, the topics discussed, materials made available to the committee, and such other matters as the study director determines should be included, except that the brief summary will not disclose the substantive content or conclusions or recommendations of any draft report or discussions thereof or disclose any report review comments.

Public Access File A public access file for a committee project is established as soon as the study director creates a project record in the National Academies’ current projects system.2

Materials provided at a data-gathering meeting or received by mail or fax from an organization or lay persons who are not officials, agents, or employees of the National Academies are placed in the public access file. Video tapes, audio tapes, or other alternative media such as diskettes or slides or viewgraphs presented to the committee by an organization or by individuals who are not officials, agents, or employees of the National Academies are considered by the National Academies to be subject to public disclosure as well.

Materials Exempt from the Public Access File The study director must request and receive advance written approval from the National Academies’ Office of General Counsel (OGC) for withholding from the public any material presented to a committee by an organization or by a person other than an official, agent, or employee of the National Academies. This request must include adequate documentation to support such withholding. For example, in the case of classified or statutorily protected information, the National Academies must receive a written statement addressed to the National Academies setting forth sufficient information to enable the National Academies’ Office of General Counsel and the National Research Council’s Executive Office to confirm that the information in question would be exempt from public disclosure under one or more of the Freedom of Information Act (FOIA)3 exemptions. The study director may not distribute to committee members any such materials (containing restrictive legends or markings limiting disclosure) without first consulting

FCC V General Information / xxiii

the OGC. Only written materials that the OGC, in consultation with the National Research Council Executive Officer, determines to be exempt from disclosure under the exemptions to the disclosure requirements of the FOIA will be withheld from the Public Access File.

Procedures for Submission and Development of Specifications

The committee will consider suggested specifications, such as previously elaborated, submitted with supporting data by any interested party, including food ingredient manufacturers and suppliers, food processors, and industry associations. Suggested specifications should be submitted, in duplicate, to Food Chemicals Codex, Food and Nutrition Board, Institute of Medicine, 500 Fifth Street, N.W., Washington, D.C. 20001. The committee and/or the project staff examine suggested specifications and often expand them to meet the general criteria the committee requires. Because committee discussions involving quality characteristics of substances used in food or food processing might result in sharing privileged or proprietary information, contributors may request that such discussions be held in closed sessions. The final outcome of such discussions must be openly shared with all manufacturers, users, and parties interested in the substance discussed; therefore, open discussions are the norm, except during unusual circumstances. Where privileged or proprietary information is concerned, the project staff can put such information in a format so that the end results are not associated with particular manufacturers or users. The committee and/or the staff draft a new monograph and send it to the originator (and to any other manufacturers of that substance that can be identified) for comment. After the draft has gone through this process and all necessary revisions have been made, the committee votes by mail ballot whether to propose these specifications for public comment. If the committee finds deficiencies, or if any questions are raised, the draft is returned to the originator and other interested parties with the committee’s comments and recommendations for improvement. Once a draft has gained committee acceptance, availability of the proposed specification for comment is announced in the Federal Register or online at <www.cfsan.fda.gov> or through notices in trade journals. This notification allows the public and other interested parties as well as manufacturers and users that may be inadvertently overlooked to provide their com-ments to the committee. Once the public comcom-ments are considered and any necessary changes made, the committee votes to determine whether the monograph is suitable for publication. Monographs as well as supporting materials such as general tests and infrared spectra are then reviewed through the National Research Council’s report review process and, if approved, are published in the next edition of the FCC or a supplement.

Procedure for Revising Specifications

xxiv / General Information FCC V

and analytical methods, comparative data for both the existing and suggested proce-dures must be submitted. Where changes in limits or other tolerances are suggested, supporting data should be presented on representative production batches. Suggestions for changing the limits of certain impurities (e.g., arsenic, cadmium, lead, fluoride, and mercury) may require the submission of safety data and information concerning the daily intake of the substance. All suggestions for revision, together with the supporting data, are reviewed by the Committee on Food Chemicals Codex and/or by the FCC staff. If other manufacturers are involved (and can be identified), they are also asked to comment. If the committee finds deficiencies, or if any questions arise, the suggested revised specifications are returned to the originator (and other manufacturers, where appropriate) with the committee’s comments or questions. If agreement cannot be reached at this point between the committee and the originator, or among manufacturers and other interested parties, a special meeting may be held to discuss the matter, or the parties involved may be invited to one of the committee’s regular meetings to examine the question in depth. Approved revisions are published either in the next edition of the FCC or in a supplement by the same procedure described underProcedures for Submission and Development of Specifications.

Additional Information

FCC users should become thoroughly familiar with theGeneral Provisionspertaining to this edition. Inquiries regarding any aspect of the operation of the FCC project may be directed to Food Chemicals Codex, Food and Nutrition Board, Institute of Medicine, 500 Fifth Street, N.W., Washington, D.C. 20001 (telephone 202-334-2580; facsimile 202-334-2316; email fcc@nas.edu). Additionally, all interested parties may view new and revised materials as presented by the Committee on Food Chemicals Codex at <www.iom.edu/fcc>.

VALIDATION OFFOOD CHEMICALS CODEXMETHODS Submissions to theFood Chemicals Codex

Submissions for new or revised specifications and analytical methods must contain sufficient information to enable committee members to evaluate the proposals. In most cases, evaluations involve assessing the clarity and completeness of the analytical methods description, determining the need for the methods, and reviewing documenta-tion that the methods have been appropriately validated. Informadocumenta-tion may vary de-pending on the type of test method involved. However, in most cases a submission will consist of the following sections:

FCC V General Information / xxv

Suggested Analytical Method Use this section to present a complete description of the analytical method sufficiently detailed to enable persons ‘‘skilled in the art’’ to replicate it. Include all important operational parameters and specific instructions such as reagent preparation, systems suitability tests performance, description of blanks used, precautions, and explicit formulas for calculating test results.

Data Elements Use this section to provide thorough and complete documentation of the validation of the analytical method. Include summaries of experimental data and calculations substantiating each of the applicable analytical performance parameters. These parameters are described in the following section.

Validation

Validation of an analytical method is the process of establishing, by laboratory studies, that the performance characteristics of the method meet the requirements for the intended analytical applications. Express performance characteristics in terms of ana-lytical parameters. Each of the recommended parameters is defined in the next section of this chapter, along with a delineation of a typical method by which it may be measured.

Typical analytical parameters used in assay validation are accuracy, precision, specificity, limit of detection, limit of quantitation, linearity, range, and ruggedness.

Accuracy

Definition The accuracy of an analytical method is the closeness of test results obtained by that method to the true value. Accuracy may often be expressed as percent recovery by the assay of known, added amounts of analyte.

Determination Determine the accuracy of an analytical method by applying that method to samples to which known amounts of analyte have been added both above and below the normal levels expected in the samples. Calculate the accuracy from the test results as the percentage of analyte recovered by the assay.

Precision

Definition The precision of an analytical method is the degree of agreement among individual test results when the procedure is applied repeatedly to multiple samplings of a homogeneous sample. The precision of an analytical method is usually expressed as the standard deviation or relative standard deviation (coefficient of variation). Precision may be a measure of the degree of either reproducibility or repeatability of the analytical method under normal operating conditions. In this context, reproducibility refers to the use of the analytical procedure in different laboratories. Intermediate precision expresses within-laboratory variation, as on differ-ent days, or with differdiffer-ent analysts or equipmdiffer-ent within the same laboratory. Repeat-ability refers to the use of the analytical procedure within a laboratory over a short time, using the same analyst with the same equipment.

xxvi / General Information FCC V

been carried through the complete analytical procedure from sample preparation to final test result.

Specificity

Definition The specificity of an analytical method is its ability to measure, both accurately and specifically, the analyte in the presence of components that may be expected to be present in the sample matrix. Specificity may often be expressed as the degree of bias of test results obtained by analysis of samples containing added impurities, degradation products, or related chemical compounds when compared with test results from samples without added substances. The bias may be expressed as the difference in assay results between the two groups of samples. Specificity is a measure of the degree of interference (or absence thereof) in the analysis of complex sample mixtures.

Determination Determine the specificity of an analytical method by comparing test results obtained from the analysis of samples containing impurities, degradation products, or related chemical compounds with those obtained from the analysis of samples without these elements. The bias of the assay, if any, is the difference in test results between the two groups of samples.

When impurities or degradation products are unidentified, demonstrate specificity by analyzing samples (with the method in question) containing impurities or degrada-tion products and by comparing the results to those from addidegrada-tional purity assays (e.g., chromatographic assay). The degree of agreement of test results is a measure of the specificity.

Limit of Detection

Definition The limit of detection is a parameter of limit tests. It is the lowest concentration of analyte in a sample that can be detected, but not necessarily quanti-tated, under the stated experimental conditions. Thus, limit tests merely substantiate that the analyte concentration is above or below a certain level. The limit of detection is usually expressed as the concentration of analyte (e.g., percentage, milligrams per gram, parts per billion) in the sample.

Determination Determining the limit of detection of an analytical method will vary depending on whether it is an instrumental or noninstrumental procedure. For instrumental procedures, different techniques may be used. Some investigators deter-mine the signal-to-noise ratio by comparing test results from samples containing known concentrations of analyte with those of blank samples and establish the minimum level at which the analyte can be reliably detected. A signal-to-noise ratio of 2:1 or 3:1 is generally accepted. Other investigators measure the magnitude of analytical back-ground response by analyzing a number of blank samples and calculating the standard deviation of this response. The standard deviation, multiplied by a factor, usually 2 or 3, provides an estimate of the limit of detection. This limit is subsequently validated by the analysis of a suitable number of samples known to be close to or at the limit of detection.

FCC V General Information / xxvii

Limit of Quantitation

Definition Limit of quantitation is a parameter of quantitative assays for low levels of compounds in sample matrices, such as impurities and degradation products in food additives and processing aids. It is the lowest concentration of analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions. The limit of quantitation is expressed as the concentration of analyte (e.g., percentage, milligram per kilogram, parts per billion) in the sample.

Determination Determining the limit of quantitation of an analytical method may vary depending on whether it is an instrumental or a noninstrumental procedure. For instrumental procedures, a common approach is to measure the magnitude of analytical background response by analyzing a number of blank samples and calculating the standard deviation of this response Multiplying the standard deviation by a factor, usually 10, provides an estimate of the limit of quantitation. This limit is subsequently validated by the analysis of a suitable number of samples known to be close to or at the limit of quantitation.

For noninstrumental methods, determine the limit of quantitation by analyzing samples having known concentrations of analyte and by establishing the minimum level at which the analyte can be detected with acceptable accuracy and precision.

Linearity and Range

Definition of Linearity The linearity of an analytical method is its ability (within a given range) to elicit test results that are directly, or by a well-defined mathematical transformation, proportional to the concentration of analyte in samples within a given range. Linearity is usually expressed in terms of the variance around the slope of the regression line (correlation coefficient), calculated according to an established mathematical relationship from test results obtained by the analysis of samples with varying concentrations of analyte.

Definition of Range The range of an analytical method is the interval between and including the upper and lower levels of analyte that have been demonstrated to be determined with precision, accuracy, and linearity using the method as written. The range is normally expressed in the same units as test results (e.g., percent, milligrams per kilogram, parts per million) obtained by the analytical method.

Determination of Linearity and Range Determine the linearity of an analytical method by mathematically treating test results obtained from analysis of samples with analyte concentrations across the claimed range of the method. The treatment is normally a calculation of a regression line by the method of least squares of test results versus analyte concentrations. In some cases, to obtain proportionality between assays and sample concentrations, the test data may have to be subjected to a mathemat-ical transformation before the regression analysis. The slope of the regression line and its variance (correlation coefficient) provide a mathematical measure of linearity; the y-intercept is a measure of the potential assay bias.

xxviii / General Information FCC V

Ruggedness

Definition The ruggedness of an analytical method is the degree of reproducibility of test results obtained by the analysis of the same samples under a variety of normal test conditions, such as different laboratories, analysts, instruments, lots of reagents, elapsed assay times, assay temperatures, and days. Ruggedness is normally expressed as the lack of influence on test results of operational and environmental variables of the analytical method. Ruggedness is a measure of reproducibility of test results under normal, expected operational conditions from laboratory to laboratory and from analyst to analyst.

Determination Determine the ruggedness of an analytical method by analyzing aliquots from homogeneous lots in different laboratories, by different analysts, using operational and environmental conditions that may differ but still are within the specified parameters of the assay. Determine the degree of reproducibility of test results as a function of the assay variables. This reproducibility may be compared to the precision of the assay under normal conditions to obtain a measure of the ruggedness of the analytical method.

Robustness

The robustness of an analytical method is a measure of the method’s capacity to remain unaffected by small, but deliberate, variations in method parameters, and it provides an indication of the method’s reliability during normal use.

Data Elements Required for Assay Validation

FCC assay procedures vary from highly exacting analytical determinations to subjec-tive evaluation of attributes. Considering this variety of assays, it is only logical that different test methods require different validation schemes. This section covers only the most common categories of assays for which validation data should be required. These categories are as follows:

Category I Analytical methods for quantitation of major components of food additives or processing aids (including preservatives).

Category II Analytical methods for determination of impurities in food additives or processing aids. These methods include quantitative assays and limit tests.

Category III Analytical methods for determination of performance characteristics (e.g., solubility, melting point).

For each assay category, different analytical information is needed. In the following table, data elements that are normally required for each assay category are listed.

FCC V General Information / xxix

Data Elements Required for Assay Validation

Assay Category II Analytical

Performance Assay Limit Assay

Parameter Category I Quantitative Tests Category III

Accuracy Yes Yes * *

Precision Yes Yes No Yes

Specificity No Yes No *

Limit of Detection Yes Yes Yes *

Limit of Quantitation No No Yes *

Linearity Yes Yes No *

Range Yes Yes * *

Ruggedness Yes Yes Yes Yes

*May be required, depending on the nature of the specific test.

GENERAL GOOD MANUFACTURING PRACTICES GUIDELINES FOR FOOD CHEMICALS4

Food chemicals and other substances employed as adjuncts in foods and as aids in food processing must meet recognized standards of performance and quality for their intended uses and applications. The requirements contained in the monographs of the FCC pertain to the characteristics of food chemicals at the time of their use.

It is not sufficient, however, for an end product merely to meet the FCC requirements. Production of food-quality chemicals is best achieved by implementing procedures that place primary emphasis on preventing defects and deficiencies. Thus, a product must be made and handled in a sanitary manner, in a way designed either to preclude the formation of undesirable by-products, or to ensure their adequate removal, as well as to prevent contamination, deterioration, mix-up and mislabeling, and the introduction of unusual or unexpected impurities.

Food chemicals are subject to applicable regulations promulgated by the responsible government agencies in countries in which FCC specifications are recognized. In the United States, for example, the pertinent regulations that deal primarily with sanitation are the ‘‘Current Good Manufacturing Practices in Manufacturing, Packing, or Holding Human Food.’’5

Beyond requirements related to sanitation, however, manufacturers, processors, packers, and distributors should establish and exercise other appropriate systems of controls throughout their operations, including food safety assurance systems such as Hazard Analysis and Critical Control Points (HACCP), where applicable, to ensure that FCC substances are safe and otherwise suitable for their intended use. These controls, together with the regulations cited above, constitute ‘‘good manufacturing practices.’’ While the

4_{These guidelines are presented for information only and are not intended to be mandatory in any sense as}

regards compliance with FCC specifications.

5_{Code of Federal Regulations,Title 21, Part 110, which may be obtained from the Superintendent of Documents,}

xxx / General Information FCC V

details of the application of the principles of good manufacturing practices to the manufac-turing, processing, packing, and distribution of food chemical substances will vary, the fundamental relevance of such principles at all stages of an operation should be recognized.

The principles of good manufacturing practices encompass such considerations as

T Systems of quality control and assurance, including self-auditing procedures.

T Clearly defined responsibilities of supervisory and other personnel, all of whom must

be qualified and adequately trained.

T Design, operation and maintenance of buildings and equipment, with attention to

housekeeping, sanitation, pest control, prevention of contamination of product, cleaning of equipment, a calibration program for all instruments and gauges, and environmentally satisfactory methods of waste disposal.

T Documentation of validation studies pertaining to the manufacturing process, laboratory

test methods, and equipment and computer applications, when any such studies are appro-priate.

T Written operational instructions that should include such items as

—General instructions and hazards. —Master manufacturing instructions. —Master packaging instructions.

—Master specifications for raw materials, in-process materials, packaging materials, labels, and finished products.

—Laboratory test methods.

—Control instrumentation and computer applications. —Labeling, holding, and distribution instructions.

T Handling and control, including the testing and approval, of raw materials, process aids,

intermediates, and finished products.

T Product containers, closures, and labeling (including the control of labels and labeling). T Laboratory and inspection controls and records (including the effect of process changes). T Reserve samples of raw materials and products.

T Written records that contain essential operational data for each individual lot of food

chemical and that permit tracing the lot history from the raw materials through manufactur-ing, packagmanufactur-ing, holdmanufactur-ing, and distributing the product.

T Product stability and lifespan.

T Systems for holding, evaluating, and disposing of rejected products and returned mate-rials.

T Procedures for investigating complaints and taking appropriate corrective action.

FCC V General Information / xxxi

Note: Depending on the processes used, it frequently is possible to divert the grade product from the main product stream as the final steps in producing a food-grade product are approached, and to complete the processing under conditions suitable for food-grade substances. In such cases, if the diverted material can be adequately characterized by a knowledge of its history, and/or by appropriate analyti-cal testing, it may be considered to be the raw material for the food-grade product.

Biotechnology (processes involving the use of biological systems) is an important source of chemicals, enzymes, and other substances used in foods and in food processing. Some food ingredients have long been made by fermentation and by enzymatic processes, but now processes involving genetically modified organisms have become a prominent emerging source of such substances.

The manufacture of food chemicals, whether it involves chemical or biological synthesis and purification, or recovery from natural materials, has a number of characteristics that must be taken into account in establishing a system of good manufacturing practice. For example, in the production of many chemicals, recycling of process liquors and recovery from waste streams are necessary for reasons of quality, economics, and environmental protection. In addition, the production of some food chemicals involves processes in which chemical and biochemical mechanisms have not been fully elucidated, and thus the methods and procedures for materials accountability usually will differ from those applicable to the manufacture of other classes of materials.

Another aspect of good manufacturing practices for food chemicals relates to the possible presence of objectionable impurities. While the limits and tests provided in the FCC are consistent with the information available to the committee regarding current methods of manufacture and common impurities that may be present, it obviously is impossible to provide limits and tests in each FCC monograph for the detection of all possible impurities because these may vary with the raw materials and the method of processing used in making the chemical. Thus, to evaluate whether other undesirable impurities may be present, the manufacturer should understand, to the best degree possible for the process at hand, the factors that contribute to the presence of impurities. Solvents as well as impurities in the raw materials and processing aids, all of which might carry into the final product, must be considered. In synthetic processes, it is necessary similarly to consider intermediates and the products of side reactions, as well as the possible formation of isomeric compounds, including epimers and enantiomorphs.

xxxii / General Information FCC V

Because of the necessity to maintain the purity and integrity of the genetic materials associated with the biotechnological process, containment6 is a particularly important consideration in preventing cross-contamination as well as the inadvertent release of biologically active materials.

Exposure of all products used in foods and food processing to foreign material contami-nation must be prevented. If objectionable impurities from any source, other than those covered by FCC requirements, are suspected to be present, good manufacturing practice requires the manufacturer to ensure that the substance is suitable for its intended applica-tions as a food chemical by applying additional tests and limits. Current analytical technol-ogy should be applied wherever possible.

6_{SeeNIH Guidelines for Research Involving Recombinant DNA Molecules, Federal Register,Vol. 51, No.}

FCC V General Information / xxxiii

MONOGRAPHS ADDED TO THEFOOD CHEMICALS CODEX, FIFTH EDITION, FROM SUPPLEMENTS 1 THROUGH 3

Supplement 1 1,3,5-Undecatriene Pork Collagen Calcium Lignosulfonate Veratraldehyde Salatrim

beta-Cyclodextrin Solin Oil

Dimethyl Dicarbonate Supplement 2 Soy Protein Concentrate Glyceryl Palmitostearate L-Carnitine Sucrose Acetate Isobutyrate

4-Hexylresorcinol Erythritol

Magnesium Phosphate, Ferric Citrate Flavors

Dibasic, Mixed Hydrates Ferrous Citrate Acetaldehyde Diethyl Acetal

Manganese Citrate Maltitol 2-Acetyl Thiazole

Olestra Menhaden Oil, Hydrogenated Allyl Phenoxy Acetate Sodium Lignosulfonate Menhaden Oil, Refined Allyl Propionate Sucrose Fatty Acid Esters Sheanut Oil, Refined Borneol

Sugar Beet Fiber 2-sec-Butyl Cyclohexanone

Vitamin K Supplement 3 Butyl 2-Methyl Butyrate

Whey Protein Concentrate Acidified Sodium Chlorite Diphenyl Ether Whey, Reduced Lactose Solutions d-Fenchone Whey, Reduced Minerals Aspartame-Acesulfame Salt Fenchyl Alcohol

Yeast, Autolyzed Curdlan Furfuryl Alcohol

gamma-Cyclodextrin 2-Furyl Methyl Ketone Flavors Polyglycerol Polyricinoleic

␻-Pentadecalactone Acid

NEW MONOGRAPHS IN THEFOOD CHEMICALS CODEX, FIFTH EDITION Allura Red Whey Protein Isolate Maltol Isobutyrate

Arabinogalactan 2-Methoxy 3-(or 5- or 6-)

Bohenin Flavors Isopropyl Pyrazine

Brilliant Blue 2,6-Dimethoxy Phenol

5H-5-Methyl-6,7-Butadiene-Styrene Rubber 3,4-Dimethyl 1,2- dihydrocyclopenta[b]pyrazine

Curdlan Cyclopentandione 5-Methyl Furfural

Erythrosine 5-Ethyl 3-Hydroxy 4-Methyl Methyl Furoate

Fast Green 2(5H)-Furanone Methyl Hexanoate

Ferrous Glycinate 3-Ethyl Pyridine Methyl Isovalerate

Hydrogenated Starch Furfuryl Mercaptan 5-Methyl 2-Phenyl 2-Hexenal Hydrolysates Geranyl Isovalerate Methyl Thiobutyrate

Indigotine 2,3-Heptandione Methyl Valerate

Sunset Yellow (Z)-3-Hexenyl Butyrate ␤-Naphthyl Ethyl Ether Tartrazine (Z)-3-Hexenyl Formate Phenyl Ethyl Cinnamate Transglutaminase Hexyl Butyrate Phenyl Ethyl Propionate

Trehalose Hexyl Hexanoate Propyl Formate

Vegetable Oil Phytosterol Isoamyl Isobutyrate Propyl Mercaptan

Esters Isobutyl Formate Salicylaldehyde

xxxiv / General Information FCC V

FORMER AND CURRENT TITLES OFFOOD CHEMICALS CODEX MONOGRAPHS

Fourth Edition Title Fifth Edition Title

Acacia Gum Arabic

Ammonium Hydroxide Ammonia Solution DL-␣-Tocopherol All-rac-␣-Tocopherol D-␣-Tocopherol Concentrate RRR-␣-Tocopherol

Tocopherols Concentrate, Mixed RRR-Tocopherols Concentrate, Mixed D-␣-Tocopheryl Acetate RRR-␣-Tocopheryl Acetate

DL-␣-Tocopheryl Acetate All-rac-␣-Tocopheryl Acetate

D-␣-Tocopheryl Acetate Concentrate RRR-␣-Tocopheryl Acetate Concentrate D-␣-Tocopheryl Acid Succinate RRR-␣-Tocopheryl Acid Succinate

MONOGRAPHS COMBINED

Fourth Edition Title Fifth Edition Title

Butadiene-Styrene 50/50 Rubber Butadiene-Styrene Rubber Butadiene-Styrene 75/25 Rubber

Contents

PREFACE . . .

xiii

GENERAL INFORMATION . . .

xix

Operating Procedures of the

Food Chemicals Codex

. . .

xix

Validation of

Food Chemicals Codex

Methods . . .

xxiv

General Good Manufacturing Practices Guidelines for Food Chemicals

. . .

xxix

Lists of New Monographs and Former and Current Titles . . .

xxxiii

Section

1

GENERAL PROVISIONS AND REQUIREMENTS APPLYING TO

SPECIFICATIONS, TESTS, AND ASSAYS OF THE

FOOD

CHEMICALS CODEX

. . .

1

2

MONOGRAPH SPECIFICATIONS . . .

9

3

FLAVOR CHEMICALS . . .

515

Specifications for Flavor Chemicals (table) . . .

517

Test Methods for Flavor Chemicals . . .

630

Gas Chromatographic (GC) Assay of Flavor Chemicals . . .

635

4

INFRARED SPECTRA . . .

637

xii / Contents FCC V

5

GENERAL TESTS AND ASSAYS . . .

827

Appendix I: Apparatus for Tests and Assays . . .

831

Appendix II: Physical Tests and Determinations . . .

834

A. Chromatography . . .

834

B. Physicochemical Properties . . .

841

C. Others . . .

854

Appendix III: Chemical Tests and Determinations . . .

859

A. Identification Tests . . .

859

B. Limit Tests . . .

861

C. Others . . .

876

Appendix IV: Chewing Gum Base . . .

892

Appendix V: Enzyme Assays . . .

896

Appendix VI: Essential Oils and Flavors . . .

929

Appendix VII: Fats and Related Substances . . .

934

Appendix VIII: Oleoresins . . .

944

Appendix IX: Rosins and Related Substances . . .

947

Appendix X: Carbohydrates (Starches, Sugars, and Related

Substances) . . .

951

Solutions and Indicators . . .

962

1

/

General Provisions and

Requirements Applying to

Specifications, Tests, and Assays

of the

Food Chemicals Codex

The General Provisions provide, in summary form, the basic policies and guidelines for the interpretation and application of the standards, tests, assays, and other specifications of the

Food Chemicals Codex and make it unnecessary to repeat throughout the book those requirements that are pertinent in numerous instances.

Where exceptions to the General Provisions are made, the wording in the individual monograph or general test chapter takes precedence and specifically indicates the directions or the intent.

TITLE OF BOOK

The title of this book, including supplements thereto issued separately, is the Food Chemicals Codex, Fifth Edition. It may be abbreviated to FCC V.

Where the term ‘‘Codex’’ is used without further qualifica-tion in the text of this book, it applies to theFood Chemicals Codex, Fifth Edition.

INQUIRIES

Inquiries regarding any aspect of the operation of the Food Chemicals Codex may be directed to the Food Chemicals Codex, Institute of Medicine, 500 Fifth Street, N.W., Wash-ington, D.C. 20001.

CODEX SPECIFICATIONS

Food Chemicals Codex specifications, comprising the De-scription,Requirements, and Tests, are presented in mono-graph form (Section 2) or tabular form (Section 3) for each substance or group of related substances. They are designed to ensure that food additives have a sufficiently high level of

1

quality to be safe under usual conditions of intentional use in foods, both directly or indirectly, or in food processing. Thus, FCC specifications generally represent acceptable levels of quality and purity of food-grade ingredients available in the United States (or in other countries in which FCC specifi-cations are recognized).

The titles of FCC monographs are in most instances the common or usual names. The FCC specifications apply equally to substances bearing the main titles, synonyms listed under the main titles, and names derived by transposition of definitive words in main titles. The Committee on Food Chemicals Codex recognizes that the nomenclature used for flavor chemicals may not be consistent with other authoritative sources.

Although the assays and tests described constitute methods upon which the specifications of theFood Chemicals Codex

depend, analysts are not prevented from applying alternative methods if they are satisfied that the procedures used will produce results of equal or greater accuracy. In the event of doubt or disagreement concerning a substance purported to comply with the requirements of this Codex, only the methods described herein are applicable and authoritative.

POLICIES AND GUIDELINES

General Policy It is the policy of the Codex to set maximum limits for trace impurities wherever they are deemed to be important for a particular food chemical, and they shall be set at levels consistent with food safety and good manufacturing practice.

2 / General Provisions and Requirements FCC V

arsenic, lead, and other heavy metals are required for flavor chemicals because of the very low levels at which these sub-stances are added to foods.

All requests to increase limits shall be considered on the basis of the toxicological risk involved, the principles of good manufacturing practice, and the availability of the same sub-stances from other sources that meet the FCC limits in question.

Added Substances (Policy) FCC specifications are in-tended for application to individual substances (single entities) and not to proprietary blends or other mixtures. Some specifi-cations, however, allow ‘‘added substances’’ (i.e., functional secondary ingredients such as anticaking agents, antioxidants, diluents, emulsifiers, and preservatives) intentionally added when necessary to ensure the integrity, stability, utility, or functionality of the primary substance in commercial use.

If an FCC monograph allows such additions, each added substance must meet the following requirements: (1) it is approved for use in foods by the U.S. Food and Drug Adminis-tration or by the responsible government agency in other countries in which FCC specifications are recognized; (2) it is of appropriate food-grade quality and meets the require-ments of theFood Chemicals Codex, if listed therein; (3) it is used in an amount not to exceed the minimum required to impart its intended technical effect or function in the primary substance; (4) its use will not result in concentrations of contaminants exceeding permitted levels in any food as a consequence of the affected FCC primary substance’s being used in food; and (5) it does not interfere with the assay and tests prescribed for determining compliance with the FCC requirements for the primary substance, unless the monograph for the primary substance has provided for such interferences. Where added substances are specifically permitted in an FCC substance, the label shall state the name(s) and amount(s) of any added substance(s).

Adding substances not specifically provided for and men-tioned by name of function in the monograph of an FCC substance will cause the substance to no longer be designated as an FCC substance. Such a combination is a mixture to be described by disclosure of its ingredients, including any that are not FCC substances.

Allergens The Committee on Food Chemicals Codex recog-nizes the issue of food allergens, but current limitations regard-ing (1) the threshold levels and (2) the analytical methods to detect allergens at very low levels have thus far prevented the inclusion in FCC monographs of specifications related to allergens.

Arsenic Specifications (Policy) Arsenic specifications will be included in monographs only when there is specific reason for the committee to believe that arsenic constitutes a likely contaminant in the substance in question.

Fluoride Limits (Guideline) The Committee on Food Chemicals Codex has established limits for fluoride